Antidiabetic Drugs

Dr Nagwa Nour EL Din

Assistant Professor
Pharmacology

Diabetes Mellitus
Chronic disorder of carbohydrate
metabolism
Results from inadequate production or
underutilization of insulin
Type 1: onset during childhood autoimmune
destruction of pancreatic B cells.
Type 2:increasing insulin resistance and
diminishing insulin secretory capacity.
frequently associated with obesity and is
much more common. usually has its onset
in adulthood

Diabetes Mellitus
Symptoms:
Hyperglycemia (Fasting blood glucose
126mg/dl)
glucosuria, polyuria, polydipsia and
polyphagia.
Without intervention, significant
complications retinopathies, glaucoma,
neuropathies, cardiovascular disease.PVD.

Anti-diabetic drugs
Insulin
Oral antidiabetic drugs

Effects of insulin (anabolic hormone)

Decrease blood glucose level by:
Increase glucose uptake by muscle and adipose tissues
Increase glucose utilization
Increase glucose storage as glycogen in liver & muscle and
inhibit glycogen breakdown

Increase lipid formation (lipogenesis )

and inhibit lipid breakdown (lipolysis)
Increase amino acid entry into the
muscle and protein synthesis

Insulin Preparations
Rapid-Acting
insulin lispro, insulin aspart, have rapid onsets and early
peaks of activity that permit control of postprandial glucose
levels. They are injected immediately before a meal.
Short-Acting
Regular insulin is used IV in emergencies or sc in
maintenance regimens, alone or mixed with intermediate- or
long-acting preparations. it requires administration 1 h or more
before a meal.
Intermediate-Acting
NPH insulin exhibits a delayed onset and peak of action is
often combined with regular and rapid-acting insulins.
Long-Acting
Insulin glargine provide a peakless basal insulin level
lasting more than 20 h, which helps control basal glucose
levels without producing hypoglycemia.

Extent & duration of action of various types

of insulin
Insulin lispro

Regular insulin

NPH insulin

Ultralente insulin

Insulin glargine

1 2 3 4 5 6 8 9 10 11 12 13 14 15 16 17 18 19 20
21 22 23 24
Time (h)

Onset

Peak

Duration

5-10min

1 hr

< 5hrs

30-45 min

2-4hrs

8hrs

Intermediate acting
NPH Insulin

2hrs

8-12hrs

Up to 24hrs

Long- acting
Insulin glargine

2hrs

Peakless

24hrs

Rapid acting
1. Insulin Lispro
2. Insulin aspart
Short -acting
Regular insulin

The daily dose of insulin includes:

0.6-0.7U/Kg/day
In obese
2U/Kg/day

WE use mixtures of Intermediate or long acting

insulin to cover basal body needs
Regular, lispro or aspart insulin is added :
1. They permit control of postprandial glucose levels
2. Intermediate & long acting insulin require several hours
to reach peak therapeutic level
The most common regimen for insulin administration Split
mixed regimen

Involves the pre-breakfast(2/3dose) and pre-supper (1/3 dose)

injection of

a mixture of regular and intermediate acting

insulin

Hazards of insulin use

A. Excessive insulin effects

1.Hypoglycem
ia
Conscious patients
Sugar or candy by mouth

Tachycardia, sweating,
Hunger pain, confusion, convulsion
and coma
Unconscious patient:
IV infusion of 50ml of
50%glucose
Or Glucagon IM

2. Overeating & obesity

B.

Lipodystrophy at injection site

Indication for the use of insulin

therapy
1. Patient with type I DM
2. Pregnant women who already have
type II DM or acquire gestational
diabetes during their pregnancy
3. Patients who have type II DM and
require
intermittent insulin administration ,
such
as during surgery or infection
4. Ketoacidosis

Oral anti-diabetic drugs

Used for treatment of type II DM
Oral antidiabetics

Sulphonylureas
Secretogogues

Biguanides
endogenous
glucose
production

Glitazones
tissue
Sensitivity to
insulin

Acrabose

Slowing rate
of Glucose
Absorption from GIT

1- Sulfonylureas
insulin release from pancreatic beta cells
1st generation
2nd generation
Glyburide
Glipizide
Adverse effects:
1- Hypoglycemia
2- appetite body weight

2- Biguanides
Metformin

hepatic Gluconeogenesis
2. glucose uptake & oxidation
3. glucose absorption from GIT
plasma glucagon level

Adverse effects:
GIT distress

Biguanides

Sulphonylureas

Metformin
endogenous G
production
No (euglycemic)

Glyburide
release of
insulin

Yes

Obese type 2 diabetes

GIT disturbances

Type 2 diabetes
Hypoglycemiaappetite

Example
Mechanism
Risk of hypoglycemia

Appetite & weight

Use
Adverse effects

3- Glitazones
(Thiazolidinediones)
Pioglitazone
Mechanism of action
Increase the sensitivity of liver, skeletal
muscle & adipose tissue to insulin

Adverse effects
1. Fluid retention & Edema
2. Anemia
3. CV risk (rosiglitazone)

4- Acarbose
Glucosidase inhibitor act in the intestine

Slow digestion of starch & Delay

absorption of glucose so
postprandial hyperglycemia is
reduced No hypoglycemia
Complex-CHO

glucosidase
Glucose

Adverse effects
GIT distress : Flatulence and diarrhea

Absorption

Sites of action of oral

hypoglycemics

Glitazones